pharmacokinetics of midazolam, dabigatran, pitavastatin, atorvastatin, and rosuvastatin in participants with renal insufficiency in the presence and absence of rifampin (mk-0000-386)

Conditions: Renal Insufficiency

Summary: the purpose of this open-label, 2-period, fixed-sequence study is to characterize the plasma pharmacokinetic profiles of midazolam, dabigatran, pitavastatin, atorvastatin, and rosuvastatin following a single oral dose administration of a microdose cocktail in healthy participants, in participants with mild, moderate, severe (not on dialysis) renal impairment, and in participants with end-stage renal disease (esrd; on dialysis).


Eligibility criteria:
inclusion criteria: all participants (with mild, moderate or severe renal impairment, end stage renal disease, or healthy): * a female must be non-pregnant, non-breast feeding and if she is of reproductive potential: must agree to use (and/or have their partner use) two acceptable methods of birth control beginning at screening, throughout the study and until 2 weeks after the last dosing of study drug * a female of non-childbearing potential: must have undergone a sterilization procedure at least 6 months prior to the first dose or be postmenopausal with amenorrhea for at least 1 year prior to the first dose * a non-vasectomized male participant must agree to use a condom with spermicide or abstain from sexual intercourse from the first dose until 90 days after the last dose of study drug * a male participant must agree not to donate sperm from dosing until 90 days after the last dose of study drug * has a body mass index (bmi) ≤ 40.0 kg/m\^2 * is a non-smoker or moderate smoker (≤ 20 cigarettes/day or the equivalent) participants with mild, moderate or severe renal impairment or end stage renal disease: * has a clinical diagnosis of renal impairment and meets the protocol-specified renal impairment function qualifications at the prestudy visit (screening) healthy participants: * has baseline creatinine clearance ≥ 90 ml/min based on cockcroft-gault equation * is judged to be in good health based on medical history, physical examination, vital signs, pulse oximetry, and laboratory safety tests exclusion criteria: all participants (with mild, moderate or severe renal impairment, end stage renal disease, or healthy): * is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study. * history or presence of clinically significant medical or psychiatric condition or disease * history of stroke, chronic seizures, or major neurological disorders * history of malignant neoplastic disease * history or presence of alcoholism or drug abuse within the past 6 months * female participant who is pregnant or lactating participants with mild, moderate or severe renal impairment: * has had a renal transplant or has had nephrectomy * has uncontrolled type 2 diabetes mellitus (t2dm), a history of type 1 diabetes, or ketoacidosis * history of significant endocrine, gastrointestinal, cardiovascular, hematological, immunological, respiratory, or genitourinary diseases participants with end stage renal disease (esrd): * had a failed renal allograft within the last 2 years prior to the first dose, or a successful renal allograft * has uncontrolled t2dm, a history of type 1 diabetes, or ketoacidosis * history of significant endocrine, gastrointestinal, cardiovascular, hematological, immunological, respiratory, or genitourinary diseases healthy participants: * history of hypoglycemia, glucose intolerance, t2dm, or ketoacidosis * history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases.